Role of the ENTH Domain in Phosphatidylinositol-4,5-Bisphosphate Binding and Endocytosis
Abstract
Endocytic proteins such as epsin, AP180, and Hip1R (Sla2p) share a conserved modular region termed the epsin NH 2 -terminal homology (ENTH) domain, which plays a crucial role in clathrin-mediated endocytosis through an unknown target. Here, we demonstrate a strong affinity of the ENTH domain for phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P 2 ]. With nuclear magnetic resonance analysis of the epsin ENTH domain, we determined that a cleft formed with positively charged residues contributed to phosphoinositide binding. Overexpression of a mutant, epsin Lys 76 → Ala 76 , with an ENTH domain defective in phosphoinositide binding, blocked epidermal growth factor internalization in COS-7 cells. Thus, interaction between the ENTH domain and PtdIns(4,5)P 2 is essential for endocytosis mediated by clathrin-coated pits.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The NH2 terminus of PICALM contains an epsin NH2-terminal homology domain for phosphatidylinositol-4,5-bisphosphate binding, which allows PICALM to sense membrane curvature and regulate the size of clathrin-coated vesicles.
“The NH2 terminus of PICALM contains an epsin NH2terminal homology domain for phosphatidylinositol-4,5bisphosphate binding, which allows PICALM to sense membrane curvature (284) and regulate the size of clathrincoated vesicles (409).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [284]
Cited by
Sorted by citations
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,294 · see citing works
The PX domains of p47phox and p40phox bind to lipid products of PI(3)K
Kanai, F., Liu, H., Field, S. J., Akbary, H., Matsuo, T., Brown, G. E., Cantley, L. C., & Yaffe, M. B. (2001) · Nature Cell Biology · doi:10.1038/35083070 · Cited by 611 · see citing works
Endocytosis and signaling: Cell logistics shape the eukaryotic cell plan
Sigismund, S., Confalonieri, S., Ciliberto, A., Polo, S., Scita, G., & Di Fiore, P. P. (2012) · Physiological Reviews · doi:10.1152/physrev.00005.2011 · Cited by 338 · see citing works
Phosphoinositides in Control of Membrane Dynamics
Schink, K. O., Tan, K.-W., & Stenmark, H. (2016) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-111315-125349 · Cited by 283 · see citing works
Molecular Circuitry of Endocytosis at Nerve Terminals
Dittman, J., & Ryan, T. A. (2009) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.042308.113302 · Cited by 238 · see citing works
PMIpred: a physics-informed web server for quantitative protein–membrane interaction prediction
van Hilten, N., Verwei, N., Methorst, J., Nase, C., Bernatavicius, A., & Risselada, H. J. (2024) · Bioinformatics · doi:10.1093/bioinformatics/btae069 · Cited by 41 · see citing works
- Authors
- Itoh, T., Koshiba, S., Kigawa, T., Kikuchi, A., Yokoyama, S., & Takenawa, T.
- Affiliations
- Institute of Medical Science, The University of Tokyo (JP)
- RIKEN (JP)
- SPring-8 (JP)
- Hiroshima University (JP)
- Corresponding author
- Takenawa, Tadaomi
- Venue
- Science
- Published
- 2001-02-09
- Volume
- 291
- Issue
- 5506
- Pages
- 1047-1051
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1977951612
- Cited by
- 469
- References
- 0
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 9 · 2023: 5 · 2022: 8 · 2021: 14 · 2020: 17 · 2019: 7 · 2018: 16 · 2017: 8 · 2016: 14 · 2015: 8 · 2014: 13 · 2013: 18 · 2012: 21
- FWCI
- 18.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- ENTH domain, epsin, phosphatidylinositol 4,5-bisphosphate, clathrin-mediated endocytosis, phosphoinositide binding, AP180, HIP1R, coated pits, protein-protein interaction
- MeSH terms
- Animals, Carrier Proteins, Chlorocebus aethiops, Clathrin, Coated Pits, Cell-Membrane, DNA-Binding Proteins, Endocytosis, Epidermal Growth Factor, Inositol Phosphates, Liposomes, Models, Molecular, Neuropeptides, Protein Conformation, Recombinant Fusion Proteins, Transcription Factors, Zinc Fingers, Protein Structure, Secondary, Protein Structure, Tertiary, Phosphatidylinositol 4,5-Diphosphate, COS Cells, Nuclear Magnetic Resonance, Biomolecular, Amino Acid Substitution, Amino Acid Motifs, Vesicular Transport Proteins, Adaptor Proteins, Vesicular Transport
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
